title: Jeb/Alk signalling regulates the Lame duck GLI family transcription factor in the Drosophila visceral mesoderm.
abstract: The Jelly belly (Jeb)/Anaplastic Lymphoma Kinase (Alk) signalling pathway regulates myoblast fusion in the circular visceral mesoderm (VM) of Drosophila embryos via specification of founder cells. However, only a limited number of target molecules for this pathway are described. We have investigated the role of the Lame Duck (Lmd) transcription factor in VM development in relationship to Jeb/Alk signal transduction. We show that Alk signalling negatively regulates Lmd activity post-transcriptionally through the MEK/MAPK (ERK) cascade resulting in a relocalisation of Lmd protein from the nucleus to cytoplasm. It has previously been shown that downregulation of Lmd protein is necessary for the correct specification of founder cells. In the visceral mesoderm of lmd mutant embryos, fusion-competent myoblasts seem to be converted to 'founder-like' cells that are still able to build a gut musculature even in the absence of fusion. The ability of Alk signalling to downregulate Lmd protein requires the N-terminal 140 amino acids, as a Lmd(141-866) mutant remains nuclear in the presence of active ALK and is able to drive robust expression of the Lmd downstream target Vrp1 in the developing VM. Our results suggest that Lmd is a target of Jeb/Alk signalling in the VM of Drosophila embryos.
authors.affiliation: Department of Molecular Biology, Building 6L, Umeå University, Umeå S-90187, Sweden.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Popichenko
authors.forename: Fredrik
authors.initials: F
authors.lastname: Hugosson
authors.forename: Camilla
authors.initials: C
authors.lastname: Sjögren
authors.forename: Murat
authors.initials: M
authors.lastname: Dogru
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Georg
authors.initials: G
authors.lastname: Wolfstetter
authors.forename: Christina
authors.initials: C
authors.lastname: Schönherr
authors.forename: Mahsa
authors.initials: M
authors.lastname: Fallah
authors.forename: Bengt
authors.initials: B
authors.lastname: Hallberg
authors.forename: Hanh
authors.initials: H
authors.lastname: Nguyen
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Palmer
mesh_terms: D021581:Active Transport, Cell Nucleus; D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D030801:Animals, Genetically Modified; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D017344:Genes, Insect; D020935:MAP Kinase Signaling System; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D008954:Models, Biological; D024510:Muscle Development; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; C524693:Mib2 protein, Drosophila; D050505:Mutant Proteins; D018006:Myogenic Regulatory Factors; D010446:Peptide Fragments; C440828:jeb protein, Drosophila; C442328:lmd protein, Drosophila; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: Alk; Drosophila; Founder cell; Fusion competent myoblast; Jeb; Lmd; Visceral muscle